Design, synthesis, and activity of 4-quinolone and pyridone compounds as nonthiol-containing farnesyltransferase inhibitors

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• 作者：Li ; Qun ; Claiborne ; Akiyo ; Li ; Tongmei ; Hasvold ; Lisa ; Stoll ; Vincent S. ; Muchmore ; Steven ; Jakob ; Clarissa G. ; et. al.
• 关键词：Farnesyltransferase inhibitors ; Anticancer ; Tipifarnib ; Quinolone ; Pyridone
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2004
• 出版时间：November 1, 2004
• 年：2004
• 卷：14
• 期：21
• 页码：5367-5370
• 全文大小：341 K

文摘

As a part of our efforts to identify potent inhibitors of farnesyltransferase (FTase), modification of the structure of tipifarnib through structure-based design was undertaken by replacing the 2-quinolones with 4-quinolones and pyridones, and subsequent relocation of the D-ring to the N-methyl group on the imidazole ring. This study has yielded a novel series of potent and selective FTase inhibitors. The X-ray structure of tipifarnib (1) in complex with FTase was described.